STK11/LKB1 Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact

The gene codes for liver kinase B1 ( ), a highly conserved serine/threonine kinase involved in many energy-related cellular processes. The canonical tumor-suppressive role for involves the activation of AMPK-related kinases, a master regulator of cell survival during stress conditions. In pre-clinical models, inactivation of leads to the progression of lung cancer with the acquisition of metastatic properties. Moreover, preclinical and clinical data have shown that inactivation of is associated with an inert tumor immune microenvironment, with a reduced density of infiltrating cytotoxic CD8 T lymphocytes, a lower expression of PD-(L)1, and a neutrophil-enriched tumor microenvironment. In this review, we first describe the biological function of and the role of its inactivation in cancer cells. We report descriptive epidemiology, co-occurring genomic alterations, and prognostic impact for lung cancer patients. Finally, we discuss recent data based on pre-clinical models and lung cancer cohorts analyzing the results of alterations on the immune system and response or resistance to immune checkpoint inhibitors.